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Anatomic Pathology Abstracts, 5/18

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Editors: Rouzan Karabakhtsian, MD, PhD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Rachel Stewart, DO, PhD, molecular genetic pathology fellow, University of Utah/ARUP Laboratories, Salt Lake City; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; and Shaomin Hu, MD, PhD, pathology resident, Albert Einstein College of Medicine, Montefiore Medical Center.

Outcomes related to use of hygroscopic sonographically detectable clips

Diagnostic efficiency in digital pathology: optical versus digital assessment

Estrogen receptor mutation in bone metastases from breast cancer

Digital image analysis of HER2 IHC in gastro-oesophageal adenocarcinomas

Categorizing and assessing gastric carcinomas with lymphoid stroma

Outcomes related to use of hygroscopic sonographically detectable clips

The use of hygroscopic sonographically detectable clips (HSDCs) has dramatically increased in recent years, especially for breast cancer patients who undergo neoadjuvant chemotherapy. The authors conducted a study to define the appearance of HSDC sites in histopathological specimens and allow pathologists to recognize these sites and differentiate them from other lesions. The authors examined 124 breast cancer specimens in which the application of HSDCs was documented—88 breast tissues and 36 lymph nodes—and analyzed the appearance of the clip sites in these tissues. Clip sites were clearly detected histologically in 79 of 88 (90 percent) breast specimens and 29 of 36 (81 percent) lymph node specimens. In 69 of the breast specimens and 23 of the lymph node specimens, the HSDC site had a specific characteristic appearance of a pseudocyst, lined by layers of epithelioid histiocytes, sometimes with pseudopapillary formation, and with minimal or no fibrosis. In other specimens, the predominant findings were scarring, scattered foamy macrophages, and abundant siderophages, which are usually found in sites of other clips. As nonpalpable breast lesions become more frequent, clips play a major role in treating breast cancer, making them an important component of the communication between radiologists, surgeons, pathologists, and oncologists. HSDCs in tissues have a characteristic appearance with an epithelioid component. Pathologists should be able to recognize this finding, differentiate it from other breast lesions, and include it in the pathology report.

Carmon M, Zilber S, Gekhtman D, et al. Hygroscopic sonographically detectable clips form characteristic breast and lymph node pseudocysts. Mod Pathol. 2018;31:62–67.

Correspondence: Dr. M. Carmon at carmonm@gmail.com

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Diagnostic efficiency in digital pathology: optical versus digital assessment

It has been shown that digital images and microscopic slides can be interpreted with comparable diagnostic accuracy. But while accuracy has been well validated, the interpretative time for digital images has scarcely been studied, and concerns about efficiency remain a major barrier to their adoption. The authors investigated the efficiency of digital pathology compared with glass slide interpretation in the diagnosis of surgical pathology biopsy and resection specimens. They pulled slides from 510 surgical pathology cases involving five organ systems—gastrointestinal, gynecologic, liver, bladder, and brain. Two validating pathologists independently confirmed the original diagnoses. Diagnostic slides were scanned using the Philips IntelliSite Pathology Solution. Each case was assessed independently on digital and optical by three reading pathologists, with a six-week or longer washout period between modalities. The reading pathologists recorded assessment times for each modality. (Digital times included time to load the case.) Diagnostic accuracy was determined based on whether a rendered diagnosis differed significantly from the original diagnosis. Statistical analysis was performed to assess for differences in interpretative times across modalities. The three reading pathologists showed comparable diagnostic accuracy across optical and digital modalities (mean major discordance rates with original diagnosis, 4.8 versus 4.4 percent, respectively). Mean assessment times ranged from 1.2 to 9.1 seconds slower on digital versus optical. The slowest reader showed a significant learning effect during the course of the study so that digital assessment times decreased over time and were comparable with optical times by the end of the series. Organ site and specimen type did not significantly influence differences in interpretative times. In summary, digital image reading times compared favorably with the reading times for glass slides across a variety of organ systems and specimen types. The mean increase in assessment time was four seconds per case. The time can be minimized with experience and may be further balanced by the improved ease of electronic chart access allowed by digital slide viewing, as well as quantitative assessments, which can be expedited on digital images.

Mills AM, Gradecki SE, Horton BJ, et al. Diagnostic efficiency in digital pathology: a comparison of optical versus digital assessment in 510 surgical pathology cases. Am J Surg Pathol. 2018;42(1):53–59.

Correspondence: Dr. Anne M. Mills at amm7r@virginia.edu

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Estrogen receptor mutation in bone metastases from breast cancer

Activating mutations of the estrogen receptor α gene (ESR1) in breast cancer can cause endocrine resistance in metastatic tumor cells. The skeleton belongs to the metastatic sides frequently affected by breast cancer. The prevalence of ESR1 mutation in bone metastasis and the corresponding phenotype are not known. The authors conducted a study in which they analyzed bone metastases from breast cancer (n=231) for ESR1 mutation. They detected activating mutations of ESR1 in 27 (12 percent) patients who were a median age of 73 years (range, 55–82 years). The most frequent mutation was p.D538G (53 percent). No mutations were found in exons 4 (K303) or 7 (S463). Lobular breast cancer was present in 52 percent of mutated cases (n = 14) and 49 percent of all samples (n = 231). Mutated cancers displayed strong estrogen receptor expression. Progesterone receptor was positive in 78 percent of the mutated cases (n = 21). Of 194 estrogen receptor-positive samples, 14 percent had ESR1 mutations. Except in one mutated case, no concurrent HER2 overexpression was noted. Metastatic breast cancer with activating mutations of ESR1 had a higher Ki-67 labeling index than primary luminal cancers (median, 30 percent; range, five–60 percent, with 85 percent of cases revealing 20 percent or more Ki-67–positive cells). Of those patients for whom information on endocrine therapy was available (n = 7), two had received tamoxifen only, four had received tamoxifen followed by aromatase inhibitors, and one had been treated with aromatase inhibitors only. The authors concluded that ESR1 mutation is associated with estrogen receptor expression and high proliferative activity and affects about 14 percent of estrogen receptor-positive bone metastases from breast cancer.

Bartels S, Christgen M, Luft A, et al. Estrogen receptor (ESR1) mutation in bone metastases from breast cancer. Mod Pathol. 2018;31:56–61.

Correspondence: Dr. H. Kreipe at kreipe.hans@mh-hannover.de

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Digital image analysis of HER2 IHC in gastro-oesophageal adenocarcinomas

The authors conducted a study to test the validity of diagnostics incorporating digital image analysis for HER2 immunohistochemistry in gastro-oesophageal adenocarcinomas as an alternative to standard diagnostics using manual scoring. The study involved 319 consecutive gastro-oesophageal adenocarcinomas—232 biopsies and 87 surgical specimens. Digital image analysis (DIA) was applied to determine HER2 IHC classification using standard breast cancer and modified gastro-oesophageal cancer (GEC) cutoffs. Four independent observers established consensus manual scores. Chromogenic in situ hybridization (CISH) was performed on all 2+ cases by manual scoring or DIA, or both. HER2 status was considered positive in 3+ and CISH-positive 2+ cases. Overall agreement between DIA and consensus manual scores was 76.5 percent (weighted κ=0.66, breast cancer cutoffs) and 85.6 percent (weighted κ=0.80, GEC cutoffs). Agreement was similar for biopsies and surgical specimens. All disagreement occurred in the manual IHC-equivocal cases. DIA resulted in a reduction in 2+ cases: 75.8 percent with breast cancer cutoffs and 46.5 percent with GEC cutoffs. HER2 status was positive in 48 (15 percent) cases with standard diagnostics and DIA using GEC cutoffs and 46 (14.4 percent) cases using breast cancer cutoffs (all with CISH in 2+ cases). Using standard diagnostics as a reference, DIA showed 93.8 percent sensitivity and 99.6 percent specificity (breast cancer cutoffs) and 97.9 percent sensitivity and 99.6 percent specificity (GEC cutoffs). The authors concluded that DIA is a reliable and feasible alternative to manual HER2 IHC scoring in gastro-oesophageal adenocarcinoma, both in biopsies and surgical specimens, leading to a reduction in 2+ cases for which subsequent in situ hybridization testing is required.

Koopman T, de Bock GH, Buikema HJ, et al. Digital image analysis of HER2 immunohistochemistry in gastric- and oesoph­ageal adenocarcinoma: a validation study on biopsies and surgical specimens. Histopathol. 2018;72:191–200.

Correspondence: B. van der Vegt at b.van.der.vegt@umcg.nl

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Categorizing and assessing gastric carcinomas with lymphoid stroma

The authors conducted a study to determine whether histologic features could help identify gastric carcinomas with lymphoid stroma associated with microsatellite instability—that is, medullary carcinomas—or Epstein-Barr virus infection (EBV; termed lymphoepithelioma-like carcinomas in other organ systems). They identified 17 solid-type gastric carcinomas with lymphoid stroma, assessed EBV and microsatellite instability (MSI) status, and compared features across groups. They also compared them with 51 solid-type colorectal adenocarcinomas. The authors found that in the stomach, EBV-associated carcinomas (n = 8) contained intratumoral germinal centers (P = .024) and eosinophils (P = .030) and lacked necrosis (P = .019) compared with MSI-associated carcinomas (n = 5) and non-EBV, non-MSI carcinomas (n = 4). In the colon, MSI-driven carcinomas (n = 40) more frequently contained intratumoral lymphocytes (P = .017) and neutrophils (P = .0050) and less often metastasized to distant sites (P = .0040) than poorly differentiated carcinomas lacking MSI (n = 11). The authors concluded that morphology may help classify gastric carcinomas with lymphoid stroma, although ancillary testing appears more reliable. The terms lymphoepithelioma-like carcinoma and medullary carcinoma should not be used interchangeably.

Gonzalez RS, Cates JM, Revetta F, et al. Gastric carcinomas with lymphoid stroma: categorization and comparison with solid-type colonic carcinomas. Am J Clin Pathol. 2017;148:477–484.

Correspondence: Dr. Raul S. Gonzalez at raul_gonzalez@urmc.rochester.edu

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